title: Transition-state charge stabilization through multiple non-covalent interactions in the guanidinium-catalyzed enantioselective Claisen rearrangement.
abstract: The mechanism by which chiral arylpyrrole-substituted guanidinium ions promote the Claisen rearrangement of O-allyl α-ketoesters and induce enantioselectivity was investigated by experimental and computational methods. In addition to stabilization of the developing negative charge on the oxallyl fragment of the rearrangement transition state by hydrogen-bond donation, evidence was obtained for a secondary attractive interaction between the π-system of a catalyst aromatic substituent and the cationic allyl fragment. Across a series of substituted arylpyrrole derivatives, enantioselectivity was observed to vary predictably according to this proposal. This mechanistic analysis led to the development of a new p-dimethylaminophenyl-substituted catalyst, which afforded improvements in enantioselectivity relative to the parent phenyl catalyst for a representative set of substrates.
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Uyeda
authors.forename: Eric N
authors.initials: EN
authors.lastname: Jacobsen
mesh_terms: D001412:Bacillus subtilis / Q000201:enzymology; D002384:Catalysis; D002826:Chorismate Mutase / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry*; D019791:Guanidine / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D004952:Esters; D011758:Pyrroles; D002826:Chorismate Mutase; D019791:Guanidine